We have several research objectives, all of them stemming from earlier observations in our laboratory. The carcinogen ethionine is negative in the Ames test and is known not to react with DNA, but does ethylate tRNA extensively. Ethionine ethylates most extensively a specific subgroup of tRNAs, tRNA2Lys. We have also found that ethionine interferes with formation of the "cap" as well as with internal methylation in mRNA. The mechanisms of these reactions will be explored. We will also study the functional attributes of ethyl tRNA2Lys in both in vitro translation and transcription systems. The mRNA methyltransferases of normal and tumor tissue will be compared. The interference with "cap" formation by ethionine prompted us to explore other agents which might act similarly. The broad spectrum antiviral agent ribavirin is effective against both DNA and RNA viruses. The common feature of both kinds of viruses is that most produce "capped" mRNAs. It was found that ribavirin is an effective inhibitor of the capping guanylation of mRNA. We had observed serendipitously that the carcinogen ethionine elevates the progesterone level in the blood of target animals, including the male rat. The elevation of progesterone was also observed by other carcinogens as widely differing in structure as thioacetamide, actinomycin D and the promoter phorbol ester. None of these agents is positive in the Ames test. Therefore, they represent a group of carcinogens and promoters in which the common physiological potency is the elevation of progesterone levels. The above listed reactions as well as the physiological mechanism of the elevation of progesterone by these carcinogens will be studied.